A 15-year-old boy who underwent liver transplantation for fulminant Wilson's disease, presented with elevated transaminases 2 months post-transplant. He had recently seroconverted from previous Epstein-Barr virus (EBV) naive status and by polymerase chain reaction (PCR) had increasing viral load copies of EBV in blood. A liver biopsy was obtained 6 weeks post-transplant, which showed isolated central perivenulitis (CP). His immunosuppresion was reduced and antiviral therapy was added with subsequent increase in liver transaminases. A second liver biopsy 6 weeks later again showed isolated CP. Subsequent further reduction in immunosuppression was followed by the appearance of portal-based moderate acute cellular rejection that was resistant to immunosuppressive treatment and rapidly evolved into ductopenic chronic rejection. This case report underlines the difficulties in interpreting isolated perivenulitis, especially in the setting of EBV seroconversion, and suggests that it may not only represent a form of acute rejection but also a predictor of rapidly progressing chronic rejection.